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In this issue
- New NRA for Ground-Based Studies in Space Radiobiology
- NASA Awards Space Radiobiology Research Grants
- Save the Date for the 23rd NASA Space Radiation Investigators’ Workshop!
- Recap of the 22nd Annual NASA Space Radiation Investigators’ Workshop
- 22nd Annual NASA Space Radiation Investigators’ Workshop Student Poster Contest
- New Paper: Cancer Risks for Missions to Near Earth Asteroid and Mars
- Tribute to Bjorn Rydberg
- Historic Photo
- NASA Announces New Software Tools for Investigators
- Space Radiation Spotlight on Janet Baulch
New NRA for Ground-Based Studies in Space Radiobiology
A new NASA Research Announcement for Ground-based Studies for the Space Radiation Program Element (SRPE) in the space radiobiology of cancer and neuronal risks has been announced. It is expected that experiments funded through this NRA will utilize the beams of high energy ions simulating space radiation at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory.
NASA Research Announcement # NNJ12ZSA001N, entitled "Ground-Based Studies in Space Radiobiology", will be available electronically on or about January 26, 2012, by opening the NASA Research Opportunities homepage and then linking through the menu listings "Solicitations" to "Open Solicitations". Step-1 proposals are due on February 29, 2012, and invited Step-2 proposals are due on May 9, 2012. Proposals are required to be submitted electronically and must be submitted by an authorized official of the proposing organization.
Participation is open to all categories of organizations, including educational institutions, industry, nonprofit organizations, NASA centers, and other Government agencies. Electronic proposals may be submitted via the NASA centers, and other Government agencies.
NASA Awards Space Radiobiology Research Grants
The Human Research Program, Space Radiation Program Element, has recently awarded research grants in response to NRA NNJ11ZSA001N: Ground-Based Studies in Space Radiobiology.
The investigators are the following:
Janet Baulch
University of Maryland
High LET Radiation Induced Carcinogenesis: Epigenetic Mechanisms in Mouse Models of Human Cancers
Xingming Deng
Emory University
Synergistic Effects of Bcl2, Cigarette Smoking and Space Radiation on Carcinogenesis
Amelia Eisch
UT Southwestern
Molecular and Cellular Mechanisms of Space Radiation-Induced Changes in Hippocampal-Dependent Behavior
Lee Goldstein
Boston University - BUMC
Effects of Space Radiation on Hippocampal-Dependent Learning and Neuropathology in Wild-Type and Alzheimer's Disease Transgenic Mice
Peter Grabham
Columbia University
Effects of Space Radiation on the Function of Human Brain Capillaries and the Blood-brain-barrier: Implications for Neurodegenerative Disorders
Amy Kronenberg
Lawrence Berkeley National Laboratory
Comparative Analysis of Charged Particle-Induced Autosomal Mutagenesis in Murine Tissue and Cells
Ian McNiece
University of Miami
The Effects of Space Radiation on Stem Cells and Vascular and Cardiac Disease
Mohan Natajaran
UT San Antonio Health Science Center
Targeting Protein Cross Talk Signaling as a Biological Predictor for Space Radiation Cancer Risk
M. Kerry O’Banion
University of Rochester
Impact of Space Radiation Induced Neuroinflammation on Alzheimer and Parkinson Disease Pathology
Michael Weil
Colorado State University
Characterization of the Tumor Spectrum Arising in HZE Ion Irradiated Outbred Mice
Save the Date for the 23rd NASA Space Radiation Investigators’ Workshop!
The 23rd Annual NASA Space Radiation Workshop is tentatively scheduled for July 8–11, 2012 in Durham, North Carolina.
The Program and Organizing Committees for the Workshop have been announced:
Program Committee
F. Cucinotta, Chair, NASA Johnson Space Center
M.H. Barcellos-Hoff, New York University
L. Goldstein, Boston University
D. Kirsch, Duke University
G. Nelson, Loma Linda University Medical Center
J. Shay, University of Texas Southwestern Medical Center
B. Stripp, Duke University
R. Ullrich, University of Texas Medical Branch
Y. Wang, Emory University
X. Zhu, Case Western Reserve University School of Medicine
Organizing Committee
F. Cucinotta, Chair, NASA Johnson Space Center
D. Kirsch, Duke University
M. Onaitis, Duke University
N. Pellis, Universities Space Research Association
F. Sulzman, Universities Space Research Association
Recap of the 22nd Annual NASA Space Radiation Investigators' Workshop
One of the largest ever annual NASA Space Radiation Workshops drew 189 attendees to South Shore Harbour Resort and Conference Center in League City, Texas, September 18–21, 2011. Due to the massive earthquake and tsunami In March in Japan, the 6th International Workshop on Space Radiation Research (IWSRR), originally scheduled from May 26–31, 2011 was postponed.
To keep from losing a year’s worth of data reporting, it was decided to forge ahead to quickly organize and hold the 22nd Annual NASA Space Radiation Investigators’ Workshop in the United States. The Program and Organizing Committees sprang into action; USRA’s Meeting and Publications Services located a venue that could accommodate the Workshop and developed a web site that communicated news to PIs and accepted abstracts.
As more abstracts were received, it became apparent that a parallel session would need to be added to accommodate additional oral talks. All in all, 70 scientific talks and 56 posters and 23 student posters were presented in a three-day workshop.
Attendees chose from sessions on stem cells and risks, space physics and technology environments, tissue specific cancer risk models, CNS models, transport codes and shielding, non-targeted effects (NTE) and high LET radiation on biological systems, acute and degenerative risks, international talks, and biological countermeasures.
Invited lectures were presented on Alzheimer’s Disease, Irradiation Effects on Stem Cells, Complications of Cytotoxic Therapy, Signaling Networks, Radiation Environment Models, and International Investigations. A special memorial lecture focused on the contributions of Professor Robert Katz and implications of the scientific field of track structure, which he originated, to radiobiological concepts applied in radiotherapy and radiation protection.
Refresher sessions on stem cell biology, systems biology, and genomics technologies were designed as “electives” to update an “up-early” audience. The dinner banquet lecture was presented by NASA Astronaut Michael L. Gernhardt, who discussed his experiences as, first, a commercial deep sea diver, and as an astronaut veteran of four space flights, including four spacewalks totaling 23 hours and 16 minutes.
The critical questions raised or discussed in each plenary session were summarized by Session Chairs:
Committees who planned and organized the Workshop were the following: Program Committee
Panel on Space Physics and Technology
Organizing Committee
Logistics Committee
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22nd Annual NASA Space Radiation Investigators' Workshop Student Poster Contest
A record number of students (23) presented posters in the Student Poster Contest. The students, who presented posters and two-minute oral talks, were judged by a record number (33) of judges as well!
Postdoctoral Fellow Contest
First Place Award
Daniela Trani, Georgetown University
“Quantitative and Qualitative Features of Intestinal Tumorigenesis Induced in Apc1638N/+ Mice by Low- and High-LET Radiation”
Second Place Award
Kim Sang, University of Texas Southwestern Medical Center
“Bardoxolon-Methyl (CDDO-Me): An Anti-Oxidant, Anti-Inflammatory Modulator is a Novel Radiation Countermeasure and Mitigator”
Third Place Award
James Jacobus, University of Iowa
“Cancer, Aging, and Gender-Based Susceptibility to Silicon and Iron Heavy Ion Exposure in Mice with Altered Mitochondrial Metabolism”
Honorable Mention
Catherine Davis, Johns Hopkins University School of Medicine
“Neurobehavioral Effects of Space Radiation on Psychomotor Vigilance”
Honorable Mention
Jonathan Tang, Lawrence Berkeley National Laboratory
“NASA Specialized Center of Research: the Contribution of Non-Targeted Effects in HZE Cancer Risk: In Silico Model”
Graduate Student Contest
First Place Award
Cristel Camacho, University of Texas Southwestern Medical Center
“Fe Irradiation Cooperates with Ink4a/Ink4b/Arf Loss to Generate High Grade Gliomas in Transgenic Mouse Models”
Second Place Award
Aadil Kaisani, University of Texas Southwestern Medical Center
“Risk Assessment of Radiation Induced Invasive Cancer in Mouse Model of Lung and Colon Cancer”
Third Place Award
Ashley Purgason, University of Texas Medical Branch
“Molecular and Histopathological Changes in Mouse Intestinal Tissue Following Whole-“Body Proton- or Gamma-Irradiation”
Special Undergraduate Recognition Award
Shannon Saganti, Houston Baptist University
“Long-Duration Human Space Expeditions and Radiation Exposure: 2000–2011”
Special Undergraduate Recognition Award
Ashley Way, Prairie View A&M University
“Human Space Exploration and Radiation Exposure from EVA: 1981-2011”
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| Student poster contest winners were recognized at the Student Poster Award Ceremony at the Workshop Banquet at space Center Houston. Pictured are (from left) Kim Sang, Aadil Kasani, James Jacobus (in the rear), Catherine Davis, Cristel Camacho, Mike Gernhardt, Daniela Trani, Jonathan Tang, and Francis Cucinotta. Ashley Purgason, Shannon Saganti, and Ashley Way are not pictured. |
New Paper: Cancer Risks for Missions to Near Earth Asteroid and Mars
A new NASA technical paper provides estimates of tissue-specific cancer incidence probabilities for exploration missions to Near Earth Asteroids and Mars. In addition, for the first-time probability of causation (PC) estimates, which represent the likelihood an observed cancer due to radiation exposure, for space missions are made. Calculations are made using the NASA 2010 Cancer projection model, which includes NASA models for radiation quality factors that represent particle track structure and uncertainty analysis of the different factors that enter into risk projection models. Age and gender-specific results for the U.S. average population and a population of never-smokers predict that most cancers observed following a 30-month Mars mission at solar minimum could be attributed to exposures to galactic cosmic rays. In contrast, for 6-month missions to the International Space Station it would be highly unlikely to attribute observed cancers to space radiation. Results show that leukemia and stomach cancer are most likely related to space radiation exposures followed by lung, colon, bladder, and liver cancers. An important conclusion from their analysis is that the NASA policy to limit the risk of exposure induced death (REID) to 3% at the 95% confidence level largely ensures that estimates of the PC for most cancer types would not reach a level of significance. The authors conclude that reducing uncertainties through radiobiological research remains the most efficient method to extend the duration of space missions and to establish efficient mitigators of cancer risks.

The figure above from the paper illustrates leukemia and solid cancer risk of exposure induced cancer (REIC) distributions as a function of the physical parameter Z*2/β2 (Z* is the cosmic ray effect charge number and beta(β) its velocity). Calculations shown are for a 30 month Mars mission including 18 month surface stay at solar minimum. The results assume a 20 g/cm2 of aluminum shielded spacecraft for a 40 year old female never-smoker (lifetime cigarette use below 100 cigarettes). The prominent spikes in the figure occur at successive values of Z2 for each GCR charge group (Z=1,2,3, … to 28) at very high energies where the velocity of GCR particles approaches the speed of light (beta=1).
By: LBNL friends and colleagues
It is with deep sadness that we mourn the loss of our colleague, mentor and friend Dr. Björn Erik Rydberg, who passed away unexpectedly on December 11, 2011. Björn had a remarkable career in the field of DNA damage and repair. His strong conceptual understanding of DNA structure and of radiation physics, combined with his gift in assay development and experimental design, gave him a special perspective on this field and a unique ability to address pivotal questions. His love for charged particle work was undeniable.
Born in Sweden on May 31, 1943, Björn earned his BA in Engineering Physics from the Royal Institute of Technology, Stockholm in 1966, and then worked at the Swedish Research Institute of National Defense, where he published his first two papers in nuclear physics. He went on to obtain his Ph.D. in Biophysics from Uppsala University in 1975. His Ph.D. degree was awarded for his analysis of radiation-induced DNA strand breakage in mammalian cells using the alkaline unwinding DNA strand separation assay [1]. Soon after Björn began using the alkaline unwinding assay, he published what is still regarded as a brilliant analysis of the theoretical basis of this technique [2]. He also immediately recognized that his assay could be used to study replication forks in mammalian cells, with the nicks between ‘Okazaki’ fragments serving as starting points for unwinding in alkali [3]. During his postdoctoral training at Yale University from 1975 to 1977, Björn used the same technique to detect radiation-induced DNA strand breaks and their rejoining in crypt cells of the mouse small intestine [4]. Upon completing his postdoc, Björn went back to Sweden to take a position in the Swedish Research Institute of National Defense where he worked from 1977 to 1980. His work there expanded to include the study of mismatch repair in E.coli, published as a series of three single-author papers. Also during this period, Björn became a docent for physical biology at Uppsala University, where he lectured until 1984. In 1980, he began a collaboration with Tomas Lindahl’s group at the University of Gothenburg in which he identified the mutagenic potential of non-enzymatic DNA methylation by S-adenosyl-L-methionine [5]. Clearly ahead of his time, he further refined the alkaline unwinding technique, improving the assay’s sensitivity [6] and allowing for high-throughput analysis with cell cycle specificity using fluorescent probes and flow cytometry [7].
In 1983, while on leave from Uppsala University, Björn worked with Gerhard Kraft’s group at the Gesellschaft für Schwerionenforschung in Darmstadt, Germany, during which time he developed his interest in high-Linear Energy Transfer (LET) radiation and radiation quality effects. In 1987 he joined the Clare Hall Laboratories in the UK, where with Peter Karran he focused his efforts on cloning and chromosomally mapping the human O6-methylguanine-DNA methyltransferase gene [8], a gene encoding a methyl-acceptor protein that removes carcinogenic, methylated lesions from the DNA.
In 1990 Björn joined Lawrence Berkeley National Laboratory (LBNL), first working with Bea Singer to identify novel enzymatic activities of a DNA gycosylase in the base excision repair pathway. He then joined the radiation biophysics program at LBNL and the groups of Priscilla Cooper and Aloke Chatterjee, taking advantage of an interdisciplinary research environment that thrived, in large part, due to his active involvement. It was during this period that Björn returned to his earlier interests in the unique properties of charged particle radiations and their interaction with DNA. Papers of particular importance in the field of high-LET radiation effects include a quantitative comparison of double-strand break (DSB) yield for X-rays versus high-LET radiation using pulsed-field gel electrophoresis (PFGE). These studies revealed unexpectedly that Relative Biological Effectiveness (RBE) values determined from DSB data were considerably smaller than RBEs calculated from parallel experiments using survival as an endpoint, and actually lower than 1.0 [9, 10]. This paradox was largely resolved by Björn with a carefully conducted new experimental approach that he designed to allow the detection of small, previously unrecognized fragments of DNA from human fibroblasts exposed to accelerated nitrogen or iron ions (LET range from 97-440 keV/µm) [11, 12]. Using this advanced analysis method he correctly defined the DSB yield by inclusion of DNA fragments below 200 kbp, and these RBE values for DSBs were significantly greater than previously reported, matching more closely to those obtained for cell survival and being in much closer agreement with theoretical calculations performed by Bill Holley and Aloke Chatterjee. In related work, calculations by Holley and Chatterjee based on the 30-nm solenoidal chromatin fiber predicted that the distribution of DNA fragment lengths induced by charged particles should be highly dependent on the approximate symmetries of the chromatin structure. Indeed, Björn experimentally detected the theoretically predicted small DNA fragments of 78-450 bp and his measurements of the discrete size classes of fragments formed allowed the team to discriminate between two proposed models for the structure of chromatin [14, 16].
Another valuable series of studies elucidating the basis for the high RBE values for high-LET radiation were initiated with Markus Löbrich, a postdoc at LBNL at that time. Together they developed an assay that combined PFGE separation of rare-cutting restriction fragments from DNA of irradiated mammalian cells with the detection of intact fragments by hybridization to allow, for the first time, the analysis of the fraction of correctly vs. incorrectly rejoined DSBs after exposure to different radiation qualities [15]. Using this assay, Björn found that the mis-rejoining frequency for X-rays was non-linear and increased significantly with dose, in keeping with cytogenetic data. In contrast, the dose dependence for mis-rejoining with high-LET particles was closer to linear, with mis-rejoining frequencies much higher than for X-rays, particularly at more biologically relevant lower doses [19].
Björn’s background in engineering physics gave him a unique ability to understand the beamline physics at the Berkeley BEVALAC and the 88-inch cyclotron, as well as the Brookhaven synchrotron, where he worked closely with the physicists to tailor the beamline to achieve the biological objectives. During the extensive period of the joint Berkeley-Colorado State University NSCORT led by Edward Gillette and Aloke Chatterjee, and again during the Berkeley NSCOR led by Mary Helen Barcellos-Hoff, he mentored many students and postdoctoral fellows, often informally, to help them understand how to design good experiments at particle accelerators, how best to implement them and how to interpret the results. It was evident that scientists from many institutions around the world thought very highly of Björn and were impressed by his creativity and attention to detail, especially the physicists at BNL who were delighted to have him there to do experiments again in the recent Fall 2011 run. It was an honor to be working there with Björn. Yet, when we made him aware of the obvious esteem in which he was held at BNL, he replied in his typical modest way “well, I’ve been around for some time”.
Björn was a highly versatile scientist, drawing on approaches from diverse disciplines including molecular biology, biochemistry, and cytogenetics. His superb experimental work was regularly accompanied by brilliant mathematical analyses of the theoretical basis of the methods used. The rigor of his science and the inordinate care he took to avoid over-interpreting his findings were among the reasons why he was held in such high regard by colleagues around the world. Over the course of his career, he published over 55 scientific papers. Björn was internationally recognized as a leading expert in the field of radiation-induced DNA strand breaks and their rejoining, with special expertise in understanding the effects of high-LET particles found in galactic cosmic rays.
As a mentor, Björn was a unique and cherished individual. He always had an open door, never made you feel less for asking, and took the time to explain complicated topics. He frequently would greet you with a slight grin, as if he were expecting you, or knew something you didn’t, which was often the case. He was not a big talker, but, when he said something, everyone knew it was always worth listening. Björn radiated a calm that made it nearly impossible to get too frustrated about a failed experiment or when things didn’t work out as planned. He had a wonderful sense of humor that often surprised people who where lucky enough to see the fun-loving side of him. He was also quite athletic, bicycling to and from work each day in Berkeley.
Björn’s passing is a profound loss for the scientific community. He was a highly knowledgeable, creative and productive scientist and, above all, an outstanding experimentalist with a deeply analytical approach. Björn was a valued colleague, mentor, friend, and he was a devoted father of Ilari and Ulrika Rydberg and loving husband of Leena Rydberg. His intelligence, quiet presence, warm demeanor, and gentle smile will be sorely missed in the halls of LBNL and at NSRL.
Selected Publications Focused on High-LET and DSB Repair:
Rydberg, B., On strand breakage of DNA in mammalian cells. Acta Univ. Upsal. 332 (1975) 1 –25 (PhD thesis summary).
Rydberg, B., The rate of strand separation in alkali of DNA of irradiated mammalian cells. Radiat. Res. 61 (1975) 274–287.
Rydberg, B., DNA unwinding in alkali applied to the study of DNA replication in mammalian cells. FEBS lett. 54 (1975) 196–200.
Rydberg, B. and Johanson, K.J., Radiation-induced DNA strand breaks and their rejoining in crypt and villous cells of the small intestine of the mouse. Radiat. Res. 64 (1975) 281–292.
Rydberg, B. and Lindahl, T., Nonenzymatic methylation of DNA by the intracellular methyl group donor S-adenosyl-L-methionine is a potentially mutagenic reaction. EMBO J. 1 (1982) 211–216.
Rydberg, B., Detection of induced DNA stand breaks with improved sensitivity in human cells. Radiat. Res. 81 (1980) 492–495.
Rydberg, B., Detection of DNA strand breaks in single cells using flow cytometry. Int. J. Radiat. Biol. 46 (1984) 521–527.
Gardner, E., Rydberg, B., Karran, P. and Ponder, B.A.J., Localization of the human O6-methylguanine-DNA methyltransferase gene to chromosome 10q24.33-qter. Genomics 11 (1991) 475–476.
Rydberg, B., Löbrich, M. and Cooper, P., DNA double-strand breaks induced by high-energy neon and iron ions in human fibroblasts. I. Pulsed field gel electrophoresis method. Radiat. Res. 139 (1994) 133–141.
Löbrich, M., Rydberg, B. and Cooper, P., DNA double-strand breaks induced by high-energy neon and iron ions in human fibroblasts. II. Probing individual NotI fragments by hybridization. Radiat. Res. 139 (1994) 142–151.
Rydberg, B., Clusters of DNA damage induced by ionizing radiation: Formation of short DNA fragments. II. Experimental Detection. Radiat. Res. 145 (1996) 200–209.
Löbrich, M., Cooper, P. and Rydberg, B., Non-random distribution of DNA double-strand breaks induced by particle irradiation. Int. J. Radiat. Biol.70 (1996) 495–503.
Rydberg, B., Löbrich, M. and Cooper, P. K., Repair of clustered DNA damage caused by high LET radiation in human fibroblasts. Physica Medica 14, suppl.1 (1998) 24–28.
Rydberg, B., Holley, W. R., Mian, I. S. and Chatterjee, A., Chromatin conformation in living cells: Support for a zig-zag model of the 30 nm chromatin fiber. J. Mol. Biol. 284 (1998) 71–84.
Löbrich, M., Cooper, P. K. and Rydberg, B., Joining of correct and incorrect ends at double-strand breaks produced by high linear energy transfer radiation in human fibroblasts. Radiat. Res. 150 (1998) 619–626.
Rydberg, B., Heilbronn, L., Holley, W.R., Löbrich, M., Zeitlin, C., Chatterjee, A. and Cooper, P.K., Spatial Distribution and Yield of DNA Double-Strand Breaks Induced by 3-7 MeV Helium Ions in Human Fibroblasts. Radiat Res. 158 (2002) 32–42.
Holley, W.R., Mian, I.S., Park, S.J., Rydberg, B. and Chatterjee, A., A model for interphase chromosomes and evaluation of radiation induced aberrations. Radiat. Res. 158 (2002) 568–580.
Antonelli, F., Belli, M., Campa, A., Chatterjee, A., Dini, V., Esposito, G., Rydberg, B., Simone, G. and Tabocchini, M. A., DNA fragmentation induced by Fe ions in human cells: shielding influence on spatially correlated damage. Adv. Space Res. 34 (2004) 1353–1357.
Rydberg, B., Cooper, B., Cooper, P.K., Holley, W.R. and Chatterjee, A., Dose-dependent misrejoining of radiation-induced DNA double-strand breaks in human fibroblasts: Experimental and theoretical study for high- and low-LET radiation. Radiat. Res. 163 (2005) 526–534.
Groesser, T., Chun, E. and Rydberg, B., Relative biological effectiveness of high-energy iron ions for micronucleus formation at low doses. Radiat. Res. 168 (2007) 675–682.
Groesser, T., Cooper, B. and Rydberg, B. Lack of bystander effects from high LET radiation for early cytogenetic endpoints. Radiat. Res. 170 (2008) 794–802.
Kurpinski, K., Jang, D.J., Bhattacharya, S., Rydberg, B., Chu, J., So. J., Wyrobek, A., Li, S. and Wang, D. Differential Effects of X-rays and High-Energy 56Fe ions on Human Mesenchymal Stem Cells. Int. J. Radiat. Oncology Biol. Phys. 73 (2009) 869–877.
Groesser, T., Chang, H., Fontenay, G., Chen, J., Costes, S.V., Barcellos-Hoff, M.H., Parvin, B., and Rydberg, B. Persistence of gH2AX and 53BP1 foci in proliferating and non-proliferating human mammary epithelial cells after exposure to g-rays or iron ions. Int. J. Radiat. Biol. 87 (2011) 696–710.
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| HISTORIC PHOTO: This group appears to be quite satisfied with the outcome of the 2000 NASA Space Radiation Investigators’ Workshop. Seated (from left) are Gail Pacetti, Gautam Badhwar, and Tonya Hardin. Standing are (from left) Greg Nelson, Francis Cucinotta, Walter Schimmerling, and Jack Miller. |
NASA Announces New Software Tools for Investigators
The NASA Space Radiation Program has developed Microsoft Windows-based software tools described below to assist researchers to model and predict risk for major solar particle events, to model beam line experiments, and to simulate ion tracks. Access and usage of these software tools is restricted to citizens of the United States and to citizens of International Space Station partner nations.
Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) Projection GUI
The NASA Baryon Transport code (BRYNTRN) and the Acute Radiation Risk (ARR) code have been combined into a user friendly Graphical User Interface (GUI) to predict organ doses and prodromal risks for major solar particle events. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission, and space biophysics researchers. The ARRBOD GUI will serve as a proof-of-concept example for future integration of other human space applications risk projection models.
GCR Event-based Risk Model (GERMcode)
The GERMcode allows scientists to model beam line experiments, such as those performed at the NASA Space Radiation Laboratory, utilizing variables for ion type, shielding materials, and sample holders. The software enables experimenters to interpret their data and to estimate the basic physical and biological output of the experiments. The software allows simulation of heavy ion beams including energy loss (LET), nuclear interactions, track structures, and Bragg curves and to integrate biological response models with physical descriptions of heavy ion beams.
Relativistic Ion Tracks (RITRACKS)
RITRACKS simulates the stochastic nature of the energy deposition of relativistic ions. It was developed to use the Monte Carlo technique to simulate a stochastic cascade of the initial physical and chemical events caused by ionizing radiation in biomolecules and cells. RITRACKS evaluates the position of ionization and the excitation processes about an ion‘s track and by the electrons liberated by the ion, and proceeds to evaluate the early temporal evolution of chemical species caused by the radiolysis of water molecules.
Persons needing access to the software must first request a NASA Johnson Space Center/USRA Software Usage Agreement Questionnaire from Kay Nute nute@dslsusra.edu . The Questionnaire must then be submitted to Dr. Myung-Hee Kim myung-hee.kim@nasa.gov , who is the Access Control Officer for the NASA Space Radiation Software Tools. Dr. Kim will send specific download instructions to the approved users. Approval to download one software tool does not automatically confer approval to download each software tool; download requests will handled separately for each software tool.
Space Radiation Spotlight on Janet Baulch
Janet E. Baulch, Ph.D.
Assistant Professor
University of Maryland School of Medicine
Department of Radiation Oncology
Baltimore, Maryland
Janet Baulch grew up in Colorado, but during her undergraduate education she migrated west to California. She knew that her academic strengths and scientific interests lay in the biological sciences, but it wasn’t until she took her first developmental biology course as an undergraduate at the California State University, Hayward, that she found a niche. The idea that a single cell had all the information needed to program an entire, complex organism fascinated her. While doing her undergraduate work Janet, by chance, landed a position in Dr. Andrew Wyrobek’s laboratory at the Lawrence Livermore National Laboratory in Livermore, California. Her work evaluating sperm aneuploidy in Andy’s lab took her from thinking just about embryogenesis to investigating germ cells and their role in development. More importantly, it got her thinking about the preconception history of the parents and how that could impact the health of the offspring. One of the benefits of working at the National Laboratory was getting to meet scientists from all over and hearing about a diverse range of research. During this time, one seminar in particular caught her attention. Dr. Lynn Wiley from the University of California, Davis, gave a talk about her work using a pre-implantation embryo chimera assay to evaluate the effects of irradiation on embryonic cell proliferation following exposure of either the embryo or of the father.
The lasting impression made by Lynn Wiley and her research led Janet to the University of California, Davis for graduate school in 1994 where she sought out Lynn to be her mentor. Janet’s dissertation research in the Developmental Biology graduate program focused on the heritable effects of paternal exposures to ionizing radiation. With Lynn, Janet demonstrated inherited effects paternal radiation exposures in pre-implantation mouse embryos and in as many as four generations of mice when eggs were fertilized by mature sperm that had been pre-meiotic spermatogonia at the time of exposure. Shortly before completing her dissertation, Janet’s plans were derailed by Lynn’s death in a small plane crash in spring of 1999. Together she and lab-mate Maude Vance completed their dissertation research and graduated in 2000 with the help of Drs. Otto Raabe and James Overstreet. After graduation Janet remained at UC Davis as a post-doctoral fellow, continuing her studies of transgenerational effects of paternal radiation exposures. In 2001 she was awarded her first grant from the Department of Energy’s Low Dose Program and was appointed to assistant professor. This DOE project evaluated the impact of ATM heterozygosity on the heritable effects of paternal exposure to low-dose ionizing radiation.
In 2005, Janet was recruited to the University of Maryland School of Medicine in Baltimore by Dr. William Morgan. Joining the Department of Radiation Oncology and Bill Morgan’s group in the Radiation Oncology Research Laboratory provided Janet with new opportunities to explore the mechanisms that she had hypothesized drove the heritable effects that she had observed in her mice. The first of these mechanisms was radiation induced genomic instability, a topic on which Bill is an internationally recognized expert. More significantly, overseeing Bill’s research introduced Janet to the NASA Space Radiation Research community. She oversaw a NASA funded project evaluating WR-1065, the active metabolite of Amifostine, a cytoprotective agent approved by the FDA as a radioprotector, for its ability to protect against the effects of high LET radiation exposure. This project demonstrated that WR-1065, the active metabolite of Amifostine, a clinically used radioprotective agent, mitigates genomic instability. Follow-up work demonstrated that this decreased genomic instability is likely due at least in part to WR-1065-mediated suppression of the homologous recombination DNA repair pathway. This paved the way for Janet’s first NASA award in 2007. This project explored the role for epigenetic mechanisms in radiation induced genomic instability. This work has contributed to the literature data regarding the effects of radiation quality on DNA methylation profiles. It is also providing DNA methylation, gene expression and miRNA profiles for cells exhibiting radiation induced genomic instability in an effort to understand the perpetuation of that instability. Building on these observations from in vitro cell culture experiments, she is now evaluating similar epigenetic effects in mice in the context of radiation quality, individual radiation sensitivity, tissue specificity and age. She has also established a collaboration with Dr. Jerry Shay at UT Southwestern Medical Center to develop epigenetic profiles for their mouse models of human lung and colon cancers. The goal for this research is to take these basic mechanistic studies and apply them to cancer research. Janet hopes to identify epigenetic modifications that establish more accurate cancer risk estimates for individuals exposed to radiation. She also hopes that this and other work from her laboratory can be applied clinically, developing biomarkers that are predictive of disease severity, radiation therapy outcomes — ultimately developing new therapeutic targets or sensitizing approaches.
Since 2009 Janet has also been fortunate enough to participate in the NASA Space Radiation Summer School giving lectures on radiation epigenetics and embryonic, fetal and heritable effects of radiation exposures. She has also worked hard to fill the large shoes of Dr. Eleanor Blakely taking on the role of Faculty Chair for Experimental Methods. Right now she is gearing up for 2012 and her fourth year in these roles.
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| At the 2011 Environmental Mutagen Society Annual Meeting in Montreal, Dr. Baulch, a member of the Council, the Chair of the Epigenetics Special Interest Group, and a Session Chair, introduces the Opening Plenary lecturer, Dr. Peter Jones, University of Southern California, Norris Comprehensive Cancer Center. | Dr. Baulch presents her NASA-funded epigenetics data on the effects of irradiation on DNA methylation at the 2008 meeting of the Radiation Research Society in Boston. |
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| Graduates of the 2010 NASA Space Radiation Summer School pose with their certificates and with several faculty members, including Dr. Baulch (on the right). | |
Selected Publications
Robbins, WA, Baulch, JE, Moore II, D, Weier, H-U, Blakey, D, Wyrobek, AJ. Three-probe fluorescence in situ hybridization to assess chromosome X, Y, and 8 aneuploidy in sperm of 14 men from two healthy groups: Evidence for a paternal age effect on sperm aneuploidy. Reproduction, Fertility, and Development. 1995; 7:799–809.
Baulch, JE, Lowe, XR, Bishop, JB, Wyrobek, AJ. Evidence for a parent-of-origin effect on sperm aneuploidy in mice carrying Robertsonian translocations as analyzed by fluorescence in situ hybridization. Mutation Research. 1996 Dec;372:269–278.
Wiley, LM, Baulch, JE, Raabe, OG, Straume, T. Impaired cell proliferation in mice that persists across at least two generations from paternal irradiation. Radiation Research. 1997 Aug;148:145–151.
Baulch, JE, Raabe, OG, Wiley, LM. Heritable effects of paternal irradiation in mice on signaling protein kinase activities in F3 offspring. Mutagenesis. 2001 Jan;16:17–23.
Baulch, JE, Raabe, OG, Wiley, LM, Overstreet, JW. Germline drift in chimeric male mice possessing an F2 component with a paternal F0 radiation history. Mutagenesis. 2002 Jan;17:9–13.
Vance, MM, Baulch, JE, Raabe, OG, Wiley, LM, Overstreet, JW. Cellular reprogramming in the F3 mouse with paternal F0 radiation history. International Journal of Radiation Biology. 2002 June;78:513–526.
Baulch, JE, Raabe, OG. Gamma irradiation of Type B spermatogonia leads to heritable genomic instability in four generations of mice. Mutagenesis. 2005 Sept;20:337–343.
Baulch, JE, Li, M-W, Raabe, OG. Effect of ATM heterozygosity on heritable DNA damage in mice following paternal F0 germline irradiation. Mutation Research. 2007 Mar;616:34–45.
Laiakis, EC, Baulch, JE, Morgan, WF. Cytokine and chemokine responses after exposure to ionizing radiation: Implications for the astronauts. Advances in Space Research. 2007;39:1019–1025.
Kovalchuk, O, Baulch, JE. Epigenetic changes and nontargeted radiation effects—is there a link? Environmental and Molecular Mutagenesis. 2008 Jan;49:16–25.
Laiakis, EC, Baulch, JE, Morgan, WF. Interleukin 8 exhibits a pro-mitogenic and pro-survival role in radiation induced genomically unstable cells. Mutation Research. 2008 Apr;640:74–81.
Dziegielewski J, Baulch JE, Goetz W, Coleman, MC, Spitz DR, Murley JS, Grdina, DJ, Morgan, WF. WR-1065, the active metabolite of amifostine, mitigates radiation-induced delayed genomic instability. Free Radical Biology and Medicine. 2008 Dec;45:1674–1681.
Sowa, M, Goetz, W, Baulch, JE, Pyles, DN, Dziegielewski, J, Yovino, S, Snyder, AR, de Toledo, SM, Azzam EI, Morgan, WF. Lack of evidence for low-LET radiation induced bystander response in normal human fibroblasts and colon carcinoma cells. International Journal of Radiation Biology. 2010 Feb;86:102–113.
Dziegielewski, J, Goetz, W, Murley, JS, Grdina, DJ, Morgan, WF, Baulch, JE. Amifostine metabolite WR-1065 disrupts homologous recombination in mammalian cells. Radiation Research. 2010 Feb;173:175–183.
Dziegielewski, J, Goetz, W, Baulch, JE. Heavy ions, radioprotectors and genomic instability: implications for human space exploration. Radiation and Environmental Biophysics. 2010 Aug;49:303–316.
Aypar, U, Morgan, WF, Baulch, JE. Radiation-induced genomic instability: Are epigenetic mechanisms the missing link? International Journal of Radiation Biology. 2011 Feb;87:179–191.
Aypar, U, Morgan, WF, Baulch, JE. Radiation-induced epigenetic alterations after low and high LET irradiations. Mutation Research. 2011 Feb;707:24–33.
Sowa, M, Goetz, W, Baulch, JE, Lewis, AJ, Morgan, WF. No evidence for a low linear energy transfer adaptive response in irradiated RKO cells. Radiation Protection Dosimetry. 2011 Feb;143:311–314.
Goetz, W, Morgan, MNM, Baulch, JE. The effect of radiation quality on genomic DNA methylation profiles in irradiated human cell lines. Radiation Research. 2011 May;175:575–587.






